A case of arrhythmic cardiomyopathy caused by rare multiple gene mutations

Figures

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  Figure 1. proband's ECG: Q-T interval prolongation, low voltage of QRS complex in limb leads (A), non-persistent ventricular tachycardia (QRS group with left bundle branch block pattern) (B). Electrophysiological: the earliest V wave measured in the chamber speed state (C). Sanger sequencing confirmed the the variants in DSP, AKAP9, LMNA genes in the proband (D).

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  Figure 2. (A,B): Proband's echocardiogram: showed whole heart enlargement, overall movement weakened, left ventricular EF45% FS23%. (C–F): CMR images of probands. (C): Cardiac short-axis LGE: delayed enhancement between the free wall of the middle left ventricle and the subepicardium of the right ventricle, and delayed enhancement between the muscular walls of the interventricular septum. (D): Right ventricular outflow tract widening: 36 mm. (E): Left and right ventricular wall multiple thinning, right ventricular wall tumor (local myocardial contradictory movement). (F): Short axis native T1: increased T1 value between subepicardial left ventricular free wall and interventricular septum muscle wall.

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  Figure 3. ECG and electrophysiological of the proband's daughter A display: frequent multi-source ventricular premature beats, low limb lead voltage (A–D). Echocardiography: enlarged left atrial ventricle, overall weakened ventricular wall motion, reduced left ventricular systolic and diastolic function, and no abnormalities in the right atrium and ventricle, left ventricular EF44% and FS22% (E–G).

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  Figure 4. The image illustrates family pedigree of three rare gene variants: c.1786G > A (LMNA: p.Asp596Asn het) heterozygous missense variant in the LMNA gene and c. in the DSP gene8187delC (DSP: p.Gln2730SerfsTer16 het) heterozygous variant, both of which were identified as suspected causative variants; AKAP9 gene c.5351A > G (AKAP9: p. His1784Arg het) heterozygous missense variant, which was identified as a variant of uncertain significance. Squares indicated male family members and circles denoted female family members. The arrow indicates the index proband. Solid black symbols in the pedigree denote individuals with a history of cardiac disease (ACM). The proband's phenotype was biventricular ACM, and the proband's daughter A (39-year-old) exhibited an ALVC phenotype. Both individuals experienced syncope episodes. No phenotypic expression or incomplete penetrance has been observed in the proband's daughter B (37-year-old) and his other offspring.